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ERC Consolidator Grants for three VIB scientists: boost for innovative research

28 November 2017

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​The European Research Council (ERC) has awarded 3 VIB scientists a consolidator grant: Anna Sablina, Sarah-Maria Fendt and Massimiliano Mazzone, all from the VIB-KU Leuven Center for Cancer Biology. These 'consolidator grants' are rewarded to scientists (PhD 7-12 years) who already showed that they are able to run their own lab. The European Research Council's grant allows them to anchor the start of a high risk/high gain program, feasible through this recognition of nearly 2 Mio€ per scientist.

ERC grantsRight from the start, VIB recognized the importance of ERC for its own mission, given our obvious synergy at the science policy level:- Frontier research- Excellence as the only selection criterion- Bottom-up, all fields- Support for the individual scientist- International peer review

Every year VIB encourages group leaders to apply for ERC grants and supports them when they do. With these three new ERC grants VIB has reached the impressive number of 50 ERC-grants.

Recognition for three VIB researchersProf. Anna Sablina focuses on understanding protein posttranslational modifications in the context of human disease. Under over 500 validated cancer genes, RAS genes still comprise the most commonly mutated oncogene family. Nonetheless, despite three decades of efforts by academia and industry no effective anti-Ras inhibitors have reached the clinic, prompting a widely accepted perception that RAS is an “undruggable” target. Prof. Sablina’s group has recently demonstrated that ubiquitylation plays a pivotal role in regulation of RAS activity. These striking initial results suggest that dysregulation of RAS ubiquitylation may be an alternative mechanism of RAS activation in human disease.

Prof. Anna Sablina (VIB-KU Leuven): “This ERC grant offers me a fantastic opportunity to unravel a conceptually novel mechanism of RAS regulation. Since ubiquitylation enzymes are druggable, I’m convinced this research will open new routes towards anti-RAS therapies and may finally have brought the holy grail of cancer research within the reach.”

Prof. Sarah-Maria Fendt goes against the current dogma that the ability of cancer cells to shape the metastatic niche is driven by transcriptional regulation. Sarah wants to prove that not transcription factors, but metabolic regulation and in particular pyruvate metabolism allows breast cancer cells to shape their environment and thereby promote their own metastatic outgrowth. She will address this potential paradigm shift in vitro and in vivo using metabolomics and 13C tracer analysis.

Prof. Sarah-Maria Fendt (VIB-KU Leuven): “My ultimate goal is to inhibit the growth of cancer cells in the metastatic niche. This grant allows us to challenge the current knowledge and perform cutting-edge research that has the potential to contribute to an increased survival of cancer patients.”

Prof. Massimiliano Mazzone wants to decipher which metabolic changes in the tumor microenvironment impede proper anti-tumor immunity and how the metabolic crosstalk between different tumor compartments contributes to immunosuppression and resistance to immunotherapy. He will be probing cancer cell and immune cell metabolism via CRISPR/Cas9 mini-pool gRNA libraries for functional in vivo screening to select metabolic mediators of resistance to immunotherapy in mouse tumor models. The selection of these mini-pools will be steered by expression data and metabolic analysis in cancer patients and mouse tumors that are refractory to immunotherapies. The selected targets will undergo extensive functional characterization in whole tumors as well as in sorted cells (cancer cells, macrophages and T cells). This will allow to identify cancer cell intrinsic metabolic mediators as well as those specifically linked to the stroma cells. Prof. Mazzone wants to identify metabolic targets that interfere with this metabolic cross talk with the ultimate goal to enhance T cell fitness and as such increase the success of immunotherapy.

Prof. Massimiliano Mazzone (VIB-KU Leuven): “This grant will give our lab the opportunity to bridge the fields of cancer biology and immunology. We are indeed endorsing cell biology and cell metabolism to overcome immunosuppression and to fight cancer. When successful, in the long run, we will be able to repurpose current drugs for a different application and to screen for new compounds that target metabolic vulnerabilities within the tumor. We expect that this novel therapeutic approach can safely abate immunosuppression and ideally lead to cancer rejection when combined with currently available immunotherapeutic agents.”